Emily McFadden

Emily earned a BS in Biochemistry and Molecular Biology from the University of Richmond in 2013. She is a PhD student in Amanda Hargrove's Lab.

Contact Information:

Email Address: emily.mcfadden@duke.edu

Research Interests:

Exploring the secondary and tertiary interactions of the HOTAIR:PRC2 complex using topological mapping and small molecule probing

Long non-coding RNAs (lncRNA) have been implicated in many cancer pathways, and it seems that every day a new clinical research paper is published presenting a novel transcript. Little research is currently being done at the molecular level on the lncRNA:protein complexes that drive these cancer processes.

One of the more well-known and studied lncRNAs is HOX Transcript Antisense Intergenic RNA (HOTAIR). This lncRNA (2,158 nts) binds the Polycomb Repressive Complex 2 (PRC2). When bound to HOTAIR, this protein complex epigenetically modifies adjacent to the HOXD locus by trimethylating Lysine 27 of Histone 3 (H3K27me3), effectively quashing the translation of tumor suppressing proteins downstream. Interestingly, PRC2 is able to bind to multiple lncRNA in addition to HOTAIR, including Xist, ANRIL, and MEG3, with varying affinity and function.

This is where my research question comes in: Without a known consensus sequence among these lncRNA, how is PRC2 able to bind these lncRNA with modular degrees of specificity while avoiding promiscuous association with all RNA? I believe the answer lies in the structure of the lncRNA:protein complexes, and intend to study lncRNA:PRC2 structures in-depth.